Marine mussels are known for their ability to bind tenaciously to such varied surfaces as rocks, pilings, and ship hulls in a wet, turbulent, and saline environment.[1, 2] These marine organisms secrete adhesive proteins as liquids that rapidly harden to form adhesive plaques, all under water, allowing them to attach themselves to various surfaces. The water-resistant adhesive characteristics of mussel adhesive proteins (MAPs) are believed to be due to the presence of 3,4-dihydroxyphenylalanine (DOPA), which is also responsible for both interfacial adhesion and rapid hardening.[3-5]
There have been numerous attempts to engineer compounds that mimic the adhesive proteins secreted by marine mussels. These methods include the extraction of natural MAPs,[6-8] the use of recombinant DNA technologies to create adhesive proteins,[9-11] and synthesis of DOPA-containing peptides using both solid-phase and solution-phase methods.[12-15] Although these MAP-mimetic adhesives demonstrate strong adhesion to various surfaces,[12, 16-19] their adhesive formulations utilize peptide backbones, which can be costly to mass-produce and have limited physical properties. Messersmith and colleagues[20-23] have recently developed a series of DOPA-modified synthetic polymeric gels that demonstrate strong water-resistant adhesion. The same research group has also prepared coatings that can repel protein and cellular adsorption by chemically coupling a MAP-mimetic peptides to antifouling synthetic polymers.[24-28]
The approach of combining synthetic polymers with DOPA and its dihydroxyphenyl derivatives (DHPD) to form DHPD-modified adhesive polymers (DHPp) may have numerous applications in clinical, dental, and industrial arenas. The general structure of DHPp is shown in FIG. 1. DHPD can impart strong water-resistant adhesion as well as rapid and controllable intermolecular curing of the adhesive polymers. Different synthetic polymers can be used to control other physical properties such as but not limited to biocompatibility, solubility, biodegradability, self-assembling ability, chemical architecture, stimulus-response ability, branching, and molecular weight. Thus these molecules can be tailored to a particular use by varying the polymer portion of the compound. Specifically, the adhesive polymers described here not only can be designed to promote adhesion between two dissimilar surfaces, they can also be designed to prevent adhesion of undesirable particles (i.e. cells, proteins bacteria, etc). Additionally, inexpensive starting materials are used for the syntheses, which allow the subsequent adhesive polymers to be prepared inexpensively and in large quantities for commercialization. Furthermore, starting materials of known biocompatibility can be used to formulate these polymers, which makes them suitable for clinical applications.
New approaches to creating adhesive polymers modified with multiple DHPD are described herein. Different synthetic methods were used to combine the adhesive moiety, DHPD, with various biocompatible, synthetic compounds to create a library of adhesive polymers that can be designed for a desired application. These multi-DHPD polymers were tested for their potential as tissue adhesives, coatings for promoting adhesion, and coatings for adhesion prevention.